It is known from Food Engineering, 1983, page 59, to coat fortified rice grains with a layer consisting of methylcellulose (MC) and hydroxypropylcellulose (HPMC), with the object of preventing premature extraction of nutrients out of the rice grain during cooking. These cellulose derivatives arc soluble at low temperature (ambient temperature and body temperature) but are not soluble at high temperature. When the rice is introduced into boiling water, the cellulose derivatives ensure that escape of the nutrients is retarded during the cooking of the rice grain and less is therefore thrown away with an excess of cooking water, while the nutrients can still be released later, for example in the body. This reverse solubility behaviour in water, hereinafter referred to as LCST (LCST=lower critical solution temperature), is known for such cellulose derivatives and other polymers.
A disadvantage of this manner of encapsulating foodstuffs and other materials is that, on contact with water or another solvent at low temperature prior to the heat treatment, the materials can escape from the encasing, since the material having the LCST is soluble at low temperature.
It is also known to use polymers with LCST behaviour such as HPMC as a coating material. This polymer has been used widely because it is a food-grade film-forming polymer. HPMC is added to lipid materials in order to produce bilayer films which have a reduced water vapour permeability (see e.g. K; amper et al, J. Food Sci., 1984, 49, 1478-1481; Hagenmaier et al, J. Agric. Food Chem., 1990, 38, 17991803). Commonly two techniques are used to produce bilayer films. The first technique is by casting a lipid layer onto a preformed dry film of HPMC. The second technique is by emulsifying a melted lipid into a solution of HPMC and drying a thin layer of the emulsion. During drying, phase separation will occur, resulting in two different layers: HPMC on the product and the lipid on the outside.
All these systems have similar disadvantages as the method described in Food Engineering, 1983, 59. When heating the system, the lipid will melt and be lost in the product, leaving only a cellulosic derivative layer, which shows a release based on Fickian diffusion.
WO 89/05634 describes a sustained-release granular solid medicament form, consisting of a core granule of an excipient material such as lactose, coated with a layer of cellulose ether (HPMC), which is insoluble in hot water. The coating layer contains the active ingredient. The coating liquid, composed of the cellulose ether (5-30% by weight) and the effective ingredient, is applied at a temperature (80.degree. C.) at which the cellulose ether is insoluble. The coated granules can be coated with a further outer layer of a wax-like material, such as paraffins, waxes, higher alcohols, etc. having a melting point between 40 and 90.degree. C. In this method the LCST-behaviour of the cellulose ether is used in the production of the medicaments. A disadvantage of this method is that it is only applicable for heat-stable ingredients.
U.S. Pat. No. 5,310,558 discloses a programmed release oral solid pharmaceutical dosage form comprising a core, containing the active ingredient, optionally subcoated by a film-forming material (HPMC) with polyethylene glycol (PEG), subsequently coated with a layer comprising a mixture of a hydrophobic material (wax), 5-20% of a non-ionic surfactant and 5-30% of a water-soluble film-forming material such as HPMC. The main function of the water-soluble film-fonning material in the hydrophobic layer is to ensure the adhesion of the hydrophobic layer on the core. Heating the described system will result in melting of the hydrophobic layer, resulting in loss of the hydrophobic material of the dosage form. The system may have a further outer enteric coating consisting of methacrylic polymer and triacetin. The system will loose most of the water barrier and the active ingredients will be promptly released into the environment.